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Infections in asplenic patients

1996; Elsevier BV; Volume: 1; Issue: 4 Linguagem: Inglês

10.1016/s1198-743x(15)60286-5

1469-0691

Peter J. Jenks, Eleri M. Jones,

Gallbladder and Bile Duct Disorders

Readers are invited to use this article as a self-assessment exercise and to update their knowledge. A 29-year-old man presented in 1994 with a short history of present illness. At the age of 6, he had had his spleen surgically removed for splenic trauma following a road traffic accident. He also had a history of rheumatic fever at the age of 10 years and had been admitted to hospital on three other occasions for trauma-related problems, including a fractured clavicle in 1977. Before this illness he had generally been fit and well. On the evening before admission he had complained of a slight headache. The following morning he awoke feeling cold and numb, with intermittent hot sweats, and his wife noticed mottling of his skin. In a short time he became very unwell and was rushed into hospital. On admission his blood pressure was unrecordable, his peripheral pulses were weak and he was only just reusable. His eyes were congested and hemorrhagic. There was no obvious source for the infection; his chest was clear and chest X-ray showed no focal abnormalities, there was no neck stiffness, and only mild generalized tenderness of the abdomen was noted. There were no records of pneumococcal immunization in the patient's notes. His wife confirmed that he was supposed to take penicillin V prophylaxis (250 mg b.d.), but was not sure whether he took the medication regularly. In view of the history of splenectomy he was immediately given 2.4 g of benzyl-penicillin, followed by cefotaxime 2 g t.d.s. He was transferred to the intensive care unit for ventilatory and inotropic support. He continued to deteriorate rapidly and developed renal failure and disseminated intra-vascular coagulopathy (DIC). Despite full supportive care he failed to improve and a little over 24 h after admission he died. Blood cultures taken on admission grew a fully sensitive Streptococcus pneumoniae. An ante-mortem blood sample was later sent for penicillin assay and no penicillin or penicilloic acid was detected. This case of pneumococcal septicemia in a previously well man illustrates how infection can rapidly progress in patients who have had their spleens removed. The patient quickly developed septic shock, multi-organ failure and DIC before dying within 36 h of becoming unwell. Splenectomv had been performed 23 years previously and this was his first episode of septicemia. There was no evidence that he had ever received pneumococcal vaccine and it seemed likely that he was not taking penicillin prophylaxis, despite this being prescribed for him. The role of the spleen in host defense has been appreciated since 1919, when Morris and Bullock concluded that its removal resulted in increased susceptibility to infection [1Morris DH Bullock FD The importance of the spleen in resistance to infection.Ann Surg. 1919; 70: 513-521Crossref PubMed Google Scholar]. The first case of overwhelming post-splenectomy infection (OPSI) was described in 1929 [2O'Donnell FJ The value of splenectomy in Banti's disease.Br Med J. 1929; I: 854Google Scholar], and awareness of this condition increased after a report in 1952 of five cases of severe infection in infants who had undergone splenectomy for hereditary spherocytosis [3King H Schumacker HB Splenic studies. I. Susceptibility to infection after splenectomy performed in infancy.Ann Surg. 1952; 136: 239-242Crossref PubMed Scopus (747) Google Scholar]. The first adult case was subsequently reported in 1969 [4Whitaker AN Infection and the spleen: association between hyposplenism, pneumococcal sepsis and disseminated intravascular coagulopathy.Med J Aust. 1969; 1: 1213-1219PubMed Google Scholar] and OPSI is now recognized as a lifelong complication of this procedure. In each of the numbered questions, at least one, and up to five, of the individual entries are correct. (The answers are at the end of this article.) Tabled 1a) Dermatitis herpetiformisTrue/Falseb) Felty's syndromeTrue/Falsec) Alcoholic liver diseaseTrue/Falsed) Essential thrombocythemiaTrue/Falsee) Splenic vein thrombosisTrue/False Open table in a new tab Tabled 1a) It is the main site of phagocytosis of circulating antigens highly opsonized with specific antibodyTrue/Falseb) It has a major role in hemopoiesis in the fetusTrue/Falsec) It is the site of final maturation of reticulocytesTrue/Falsed) It is important in regulation of the circulating blood volumeTrue/Falsee) It is an important site of T-cell maturationTrue/False Open table in a new tab Tabled 1a) Reduced production of specific IgMTrue/Falseb) Reduced memory B-cell responsesTrue/Falsec) Reduced immune response to polysaccharide antigensTrue/Falsed) Reduced IgE-mediated mast cell degranulationTrue/Falsee) Reduced selection of high-affinity, antigen-specific, B-cell clonesTrue/False Open table in a new tab Tabled 1a) Mortality is around 15%True/Falseb) The overall incidence is 10% per yearTrue/Falsec) The risk of serious infection is highest in the first 2 years after splenectomyTrue/Falsed) It is more common when splenectomy is performed for Hodgkin's lymphoma than for traumaTrue/Falsee) Is more common when splenectomy is performed in children less than 5 years oldTrue/False Open table in a new tab Tabled 1a) Plasmodium falciparumTrue/Falseb) Capnocytophaga canimorsusTrue/Falsec) Streptobacillus moniliformisTrue/Falsed) Babesia bovisTrue/Falsee) Pneumocystis cariniiTrue/False Open table in a new tab Tabled 1a) Immunization is particularly important in children less than 2 years oldTrue/Falseb) Protective antibody levels wane more rapidly in asplenic patientsTrue/Falsec) Pneumococcal revaccination should be performed every 2 yearsTrue/Falsed) Vaccination against Neisseria meningitidis serotypes A, B and C is recommendedTrue/Falsee) Most asplenic patients mount an adequate immunologic response to the conjugate Haemophilus influenzae type b (Hib) vaccineTrue/False Open table in a new tab Tabled 17. With regard to antibiotic prophylaxis in asplenic patientsa) It is especially important in children under 2 years of ageTrue/Falseb) It is contraindicated in patients with coexistent immunosuppressive diseaseTrue/Falsec) Resistance among potential pathogens is an increasing problemTrue/Falsed) It should be lifelongTrue/Falsee) It is not needed if the patient has been shown to have protective levels of antibody after immunizationTrue/False Open table in a new tab Surgical removal of the spleen is essential in the management of patients with splenic rupture following trauma. Although total splenectomy is recognized to be safer, a number of conservative surgical approaches have been advocated to preserve some immunologic function. Partial splenectomy is the best alternative, and the degree of protection from OPSI appears to be proportional to the percentage of splenic tissue preserved [5Martin LW Autologous splenic transplantation.Ann Surg. 1994; 219: 223-224Crossref PubMed Scopus (85) Google Scholar]. Autotransplantation (usually in the omental pouch) and splenosis (regeneration of splenic tissue that has seeded to the peritoneum during trauma) have both been investigated, but the presence of such tissue does not imply reliable immune function and overwhelming infection has been associated with these procedures [6Holdsworth RJ Regeneration of the spleen and splenic autotransplantation.Br J Surg. 1991; 78: 270-278Crossref PubMed Scopus (62) Google Scholar]. Splenectomy may also be indicated for a number of hematologic conditions, which include the hemolytic anemias (especially hereditary spherocytosis), ideopathic thrombocytopenic purpura, hairy cell leukemia and thalassemia major. Improved imaging techniques have reduced its role as a staging procedure for lymphomas. Splenectomy is also performed in some patients with Gaucher's disease. Congenital hyposplenia is rare and is associated with malformations of the heart and gut. Functional hyposplenism is associated with a number of conditions, including sickle cell disease and essential thrombocythemia, in which reduced function is due to vascular occlusion and autoinfarction of the organ. Hyposplenism is present in 10–15% of patients with coeliac disease and it is also found in the associated condition dermatitis herpetiformis. Reduced function has also been reported in systemic lupus erythematosus, amyloid, inflammatory bowel disease, alcoholic liver disease and graft-versus-host disease complicating bone marrow transplantation. Steroids and chemotherapeutic agents also cause hyposplenism by suppressing the lymphoid white pulp. Felty's syndrome is the association of rheumatoid arthritis, splenomegaly and neutropenia, while splenic vein thrombosis results in portal hypertension and secondary enlargement of the spleen. Neither condition results in functional hyposplenism. The spleen has two distinct histologic components: the erythroid red pulp and the lymphoid white pulp. The red pulp consists of a reticular meshwork (the cords of Billroth) and sinuses which are lined with endothelial macrophages. During their passage through the red pulp, normal erythrocytes, which are deformable, are able to pass through the intraendothelial slits in the sinus wall and return to the peripheral circulation, while old, damaged and parasitized red blood cells become trapped in the cords and are destroyed. The red pulp is also the main filter of blood-borne antigens and is important in the phagocytosis of immune complexes and encapsulated bacteria such as Streptococcus pneumoniae [7Rosse WF The spleen as a filter.N Engl J Med. 1987; 317: 704-706Crossref PubMed Scopus (49) Google Scholar]. The phagocytosis of bacteria by the splenic micro-vasculature occurs after deactivation and opsonization by complement (particularly C3) and, to a lesser extent, by antibodies to form immune complexes. These are then taken up by the periarterial macrophages, which bear specialized complement and immunoglobulin Fc receptors [8Davies KA Erlendsson K Beynon HL et al.Splenic uptake of immune complexes in man is complement-dependent.J Immunol. 1993; 151: 3866-3873PubMed Google Scholar]. Because of the efficiency of this filtering system and the slow passage of blood through the spleen, which maximizes contact with phagocytic cells, the degree of opsonization needed for removal is relatively low [9Hosea SW Brown EJ Hamburger M Frank MM Opsonic requirements for intravascular clearance after splenectomy.N Engl J Med. 1981; 304: 245-250Crossref PubMed Scopus (154) Google Scholar]. The spleen is therefore crucial in the clearance of organisms early in the course of an infection before specific antibody production is fully established and is also important in removing bacteria opsonized with complement alone [10Hazelwood M Kumararatne DS The spleen? Who needs it anyway.Clin Exp Immunol. 1992; 89: 327-329Crossref PubMed Scopus (18) Google Scholar]. After splenectomy, the macrophages of the liver and other lymphoid organs are partially able to take over this function, but require higher levels of specific antibody to facilitate clearance [9Hosea SW Brown EJ Hamburger M Frank MM Opsonic requirements for intravascular clearance after splenectomy.N Engl J Med. 1981; 304: 245-250Crossref PubMed Scopus (154) Google Scholar]. The red pulp has a minor role in hemopoiesis in the human fetus from 12 weeks of gestation. Although this function is lost soon after birth, extramedullary hemopoiesis can be reactivated under conditions of hematologic stress. Sequestration of reticulocytes is also an important function and these complete their final 2 to 3 days of maturation in the cords of Billroth. Up to 45% of the total platelets may be also be sequestered in the spleen, and can be mobilized and released when needed. Although the spleen has a significant physiologic role in the regulation of the blood volume in dogs, this function is not important in humans. The lymphoid white pulp consists of the central splenic arterioles surrounded by lymphoid tissue. Immediately surrounding the central arterioles is the periarteriolar lymphatic sheath, which is densely populated with small T-lymphocytes and dendritic antigen-presenting cells (interdigitating cells). At intervals along the sheath are the Malpighian bodies, which structurally resemble lymphoid follicles, and these are surrounded by the marginal zone. Both areas mainly consist of recirculating B-lymphocytes. After B-cell activation by an antigen, a germinal center of rapidly dividing cells forms in the center of the follicle and high-affinity, antigen-specific B-cell clones are selected [11Klaus GG Kunkle A The role of germinal centres in the generation of immunological memory.in: Klaus GG Kunkle A Microenvironment in haemopoietic and lymphoid differentiation. Pitman Medical, London1981: 125-280Crossref Google Scholar]. During the primary humoral response the white pulp is therefore an important site of specific IgM production [12Lockwood CM Immunological functions of the spleen.Clin Haematol. 1983; 12: 449-465PubMed Google Scholar]. The response is maintained by the follicular dendritic cells, which can take up and retain antigens in the form of immune complexes for prolonged periods of time [13Timens W Lemans R Splenic autotransplantation and the immune system.Ann Surg. 1992; 215: 256-260Crossref PubMed Scopus (69) Google Scholar] and hence promote production of late-phase antibodies and the development of a memory response [11Klaus GG Kunkle A The role of germinal centres in the generation of immunological memory.in: Klaus GG Kunkle A Microenvironment in haemopoietic and lymphoid differentiation. Pitman Medical, London1981: 125-280Crossref Google Scholar]. The spleen has a pivotal role in the host's response to encapsulated organisms. Although this response is independent of the actual presence of T-cells, it requires T-cell-produced factors and is known as the thymus-independent antigen type 2 (TI-2) response [14Mosier DE Subbarao B Thymus-independent antigens: complexity of B-lymphocyte activation revealed.Immunol Today. 1982; 3: 217-222Abstract Full Text PDF PubMed Scopus (190) Google Scholar]. Specialized macrophages within the marginal zone are capable of taking up carbohydrate antigens such as capsular polysaccharides and initiating the TI-2 response [15Kamaratne DS Bazin H MacLennan IC Marginal zones: the major B cell compartment in rat spleens.Eur J Immunol. 1981; 11: 858-864Crossref PubMed Scopus (110) Google Scholar]. B-cells within the marginal zone produce antibodies (mainly IgM and IgG2) to polysac-charide antigens and these are important for the opsonization and phagocytosis of encapsulated organisms [16Amlat PL Grennan D Humphrey JH Splenic dependence of the antibody response to thymic independent (TI-2) antigens.Eur J Immunol. 1985; 15: 508-512Crossref PubMed Scopus (113) Google Scholar]. It has been shown that the maturation of marginal zone B-cells coincides with the ability to make antibodies to carbohydrate antigens [17Timens W Boes A Rozeboom-Ulterwijk T Poppema S Immaturity of the human splenic marginal zone in infancy.J Immunol. 1989; 143: 3200-3206PubMed Google Scholar]. Children under the age of 2 years are unable to synthesize adequate IgG2 and hence respond poorly to poly-saccharide vaccines [18Rynnel-Dagoo B Freijd A Hammarstrom L Oxelius V Persson MA Smith CI Pneumococcal antibodies of different immunoglobulin subclasses in normal and IgG subclass deficient individuals of various ages.Acta Oto-laryngol (Stockh). 1986; 101: 146-151Crossref PubMed Scopus (23) Google Scholar]. Splenectomy significantly reduces the reservoir of polysaccharide responsive B-cells and although there are small numbers of these cells in other lymphoid organs, there are not sufficient to restore full immunologic function [19Gray D Chassoux D MacLennan IC Bazin H Selective depression of thymus independent anti-DNP antibody response induced by adult but not neonatal splenectomy.Clin Exp Immunol. 1985; 60: 78-86PubMed Google Scholar]. Therefore, removal of the spleen not only results in the loss of the most important filter of encapsulated organisms, but also reduces the main immunologic response to their polysaccharide antigens. This effect is particularly significant in children, who have lower pre-existing immunity to these organisms. The spleen also produces two important opsonins [20Eichner ER Splenic function: normal, too much, and too little.Am J Med. 1979; 66: 311-320Abstract Full Text PDF PubMed Scopus (126) Google Scholar]. Tuftsin is a tetrapeptide that increases Fc-dependent phagocytosis in polymorphonuclear leukocytes and increases the activity and migration of phagocytes, and properdin is a component of the alternative complement pathway. Specific cells in the spleen also process and present antigens to splenic T-cells, and hence the delayed-type hypersensitivity reaction is reduced in splenectomized patients, as is overall T-cell function. It is not, however, an important site for T-cell maturation, as T-cells develop almost exclusively in the thymus. The spleen has no role in IgE-mediated immune responses. A number of infections are more common in splenectomized patients, but OPSI is a distinct clinical syndrome characterized by its rapid onset and fulminant progression. Clinical features include septicemia in the absence of a focus, coma, multiple organ failure, disseminated intravascular coagulopathy and bilateral adrenal hemorrhage, and mortality exceeds 50% in most series [21Van Wyck DB Overwhelming postsplenectomy infection (OPSI): the clinical syndrome.Lymphology. 1983; 16: 107-114PubMed Google Scholar]. The overall risk of OPSI is small, and a recent study estimated the incidence of severe late post-splenectomy infection to be 0.42 per 100 person years (i.e. one patient will develop severe sepsis once in 238 years) [22Cullingford GI Watkins DN Watts AJ Mallon DF Severe late post-splenectomy infection.Br J Surg. 1991; 78: 716-721Crossref PubMed Scopus (236) Google Scholar]. The incidence of overwhelming infection is dependent on underlying disease, and patients with underlying hematologic disorders, such as the lympho-reticular malignancies and thalassemia, are particularly at risk [22Cullingford GI Watkins DN Watts AJ Mallon DF Severe late post-splenectomy infection.Br J Surg. 1991; 78: 716-721Crossref PubMed Scopus (236) Google Scholar]. The incidence is lowest for splenectomy performed after trauma, and it has been suggested that splenic removal in this group is associated with minimal increased risk of infection [23Holdsworth RJ Irving AD Cuschieri A Postsplenectomy sepsis and its mortality rate: actual versus perceived risks.Br J Surg. 1991; 78: 1031-1038Crossref PubMed Scopus (410) Google Scholar]. Although the absence of a spleen in an otherwise immunocompetent adult is certainly compatible with a healthy life, it has to be remembered that the risk of rapidly progressive life-threatening disease remains in all patients. OPSI is also more common in children, and those under 5 years of age are particularly at risk [23Holdsworth RJ Irving AD Cuschieri A Postsplenectomy sepsis and its mortality rate: actual versus perceived risks.Br J Surg. 1991; 78: 1031-1038Crossref PubMed Scopus (410) Google Scholar]. In all patients the risk of OPSI is greatest in the early postoperative period, and most infections occur in the first 2 years after operation [24Pimpl W Dapunt O Kaindl H Thalhamer J Incidence of septic and thromboembolic-related deaths after splenectomy in adults.Br J Surg. 1989; 76: 517-521Crossref PubMed Scopus (104) Google Scholar]. However, infections have been reported 25 years after surgery, and the risk is generally considered to be lifelong [25O'Neal BJ McDonald JC The risk of sepsis of the asplenic adult.Ann Surg. 1981; 194: 775-778Crossref PubMed Scopus (153) Google Scholar]. Overwhelming infection after splenectomy is usually due to Streptococcus pneumoniae (∼50% of cases), Haemophilus influenzae or Neisseria meningitidis [26Ellison EC Fabri PJ Complications of splenectomy: aetiology, prevalence and management.Surg Clin North Am. 1983; 63: 1313-1330PubMed Google Scholar]. Infections with Escherichia coli, Pseudomonas aeruginosa, β-hemolytic streptococci and certain viruses, including influenza, are also more common in these patients. Capnocytophaga canimorsus (previously known as dysgonic fermenter 2) bacteremia often results in fulminant sepsis in asplenic patients [27Hickin H Verghese A Alvarez S Dysgonic fermenter 2 septicaemia.Rev Infect Dis. 1987; 9: 884-890Crossref PubMed Scopus (69) Google Scholar]. This has led to the recommendation that such patients avoid dog bites and scratches, and that, if exposure does occur, empirical treatment with amoxycillin/clavulanate or erythromycin should be started [28Morgan MS Cruikshank JG Prevention of postsplenectomy sepsis.Lancet. 1993; 341: 700-701Abstract PubMed Scopus (5) Google Scholar]. The spleen is important in the host response to malaria; as well as removing parasitized red cells, it is also the site of production of antimalarial antibodies and is involved in the cellular response to the parasite [29Wyler DJ Oster CN Quinn TC The role of the spleen in malaria infection.in: Role of the spleen in the immunity of parasitic diseases. UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Schwabe & Co., Basel1983: 183-204Google Scholar]. Increased susceptibility of asplenic patients to malaria has recently been confirmed in a large study in Papua New Guinea [30Boone KE Watters AK The incidence of malaria after splenectomy in Papua New Guinea.Br Med J. 1995; 311: 1273Crossref PubMed Scopus (49) Google Scholar]. Patients traveling to malarious areas need to be aware of this risk, and the importance of chemoprophylaxis and prevention of exposure to mosquitoes should be emphasized. In most cases, avoidance of endemic areas is preferable, whatever the reason for travel. Geoffrey Boycott, the British cricketer, who had a splenectomy at the age of 7 years after falling off some railings onto a mangle, decided not to participate in England cricket tours to the Indian subcontinent because of the potential risk of serious infection [31Boycott G Boycott: The autobiography. London Corgi Books, 1993Google Scholar]. Splenectomized patients are also more susceptible to babesiosis, an intraerythrocytic protozoal infection transmitted by Ixodes ticks [32Rossner R Zarrabi MH Benach JL Hubicht GS Babesiosis in splenectomised adults: review of 22 reported cases.Am J Med. 1984; 76: 696-701Abstract Full Text PDF PubMed Scopus (153) Google Scholar]. In Europe all nine reported cases have been in splenectomized patients and have been of the bovine type (Babesia bovis and Babesia divergens), with the majority of patients dying of a fulminant febrile hemorrhagic disease [33Dammin GJ Spielman A Benach JL Piesman J The rising incidence of clinical Babesia microti infection.Hum Pathol. 1981; 12: 398-400Abstract Full Text PDF PubMed Scopus (79) Google Scholar]. In the USA the rodent strain, Babesia microti, predominates, but only 30% of cases have been associated with asplenia, and most patients have survived [33Dammin GJ Spielman A Benach JL Piesman J The rising incidence of clinical Babesia microti infection.Hum Pathol. 1981; 12: 398-400Abstract Full Text PDF PubMed Scopus (79) Google Scholar]. Immunization aims to reduce the risk of overwhelming infection due to encapsulated organisms, and a significant reduction in medium-term pneumococcal infections has been observed in Danish children immunized with polyvalent pneumococcal vaccine after splenectomy [34Konradsen HB Henrichsen J Pneumococcal infection in splenectomised children are preventable.Acta Paediatr Scand (Stockh). 1991; 80: 423-427Crossref PubMed Scopus (75) Google Scholar]. The currently available pneumococcal vaccine (Pneumovax 23) covers 23 serotypes responsible for over 80% of bacteremic pneumococcal disease, and provides protective antibody in ∼95% of eusplenic patients [35Shapiro ED Berg A Aubren R et al.The protective efficacy of polyclonal pneumococcal polysaccharide vaccine.N Engl J Med. 1991; 325: 1453-1460Crossref PubMed Scopus (862) Google Scholar]. Most immunocompetent asplenic adults have an intact antibody response to polysaccharide vaccines, and the response to Pneumovax in this group is at least 85% [36Bolan G Broome CV Fracklam RR Plikaytis BD Fraser DW Schlech WF Pneumococcal vaccine efficacy in selected populations in the United States.Ann Intern Med. 1986; 104: 1-6Crossref PubMed Scopus (162) Google Scholar]. To optimize the response, vaccination should be carried out at least 2 weeks before surgery, but in emergency cases the vaccine may be given in the immediate postoperative period [37Caplan ES Boltansky H Snyder MJ et al.Response of traumatised splenectomised patients to immediate vaccination with polyvalent pneumococcal vaccine.J Trauma. 1983; 23: 801-805Crossref PubMed Scopus (43) Google Scholar]. The response to immunization after splenectomy is impaired in patients with altered immune function and is particularly poor in patients with hematologic malignancies treated with chemotherapy and radiotherapy. Improved results can be achieved if vaccination is carried out 2 weeks before immunosuppressive therapy is started [38Shildt RA Boyd JF McCraete JD et al.Antibody response to pneumococcal vaccine in patients with solid tumours and lymphomas.Med Paediatr Oncol. 1983; 11: 305-309Crossref PubMed Scopus (13) Google Scholar], Immunization is particularly important in children, who will have had limited previous exposure to encapsulated organisms, but should be delayed until after 2 years of age, as before this the response to polysaccharide vaccines is minimal [17Timens W Boes A Rozeboom-Ulterwijk T Poppema S Immaturity of the human splenic marginal zone in infancy.J Immunol. 1989; 143: 3200-3206PubMed Google Scholar]. It is well recognized that induced antibody levels wane more rapidly in asplenic individuals, and consequently revaccination in the United Kingdom is recommended every 5 to 10 years [39Department of Health Immunisation against infectious diseases. HMSO, London1992Google Scholar]. Newer recommendations, for the relicensed vaccine (Pneumovax II), advise revaccination of high-risk children after 3 to 5 years but not within 3 years [40Graham RC Long term management after splenectomy: has been amended [letter].Br Med J. 1994; 308: 133Crossref PubMed Scopus (3) Google Scholar]. Although earlier boosting has been advocated by some authors, revaccination in the presence of high antibody levels can be associated with adverse side effects, including local erythema, pain and serum sickness [41Obaro S Henderson DC Monteil M Long term management after splenectomy: monitor antibody levels after vaccination [letter].Br Med J. 1994; 308: 338-339Crossref PubMed Scopus (4) Google Scholar]. It has therefore been suggested that specific antibody levels should be monitored annually to determine the most appropriate time for revaccination and that assays for opsonizing activity should be used to assess their functional ability to stimulate phagocytosis [41Obaro S Henderson DC Monteil M Long term management after splenectomy: monitor antibody levels after vaccination [letter].Br Med J. 1994; 308: 338-339Crossref PubMed Scopus (4) Google Scholar]. Unfortunately, such assays are not widely available. It is hoped that with the development of new conjugate vaccines efficacy will improve in all patient groups and guidelines on the timing of revaccination will become clearer. Most centers also recommend vaccination against H. influenzae type b, N. meningitidis serogroups A and C and influenza. Asplenic patients without underlying disease have been shown to achieve protective antibody levels when immunized with the current Hib conjugate vaccine [42Ambrosino DM Lee MY Chen D Shamberger RC Response to Haemophilus influenzae type b conjugate vaccine in children undergoing splenectomy.J Pediatr Surg. 1992; 27: 1045-1047Abstract Full Text PDF PubMed Scopus (11) Google Scholar] and obtain similar responses to healthy individuals with the current bivalent meningococcal vaccine (A and C) [43Ruben FL Hawkins WA Zeigler Z et al.Antibody response to meningococcal polysaccharide vaccine in adults without a spleen.Am J Med. 1984; 76: 115-121Abstract Full Text PDF PubMed Scopus (41) Google Scholar]. Type B meningococcus, which causes the majority of invasive disease, is not covered by the current vaccine owing to the reduced immunogenicity of the type B polysaccharide [43Ruben FL Hawkins WA Zeigler Z et al.Antibody response to meningococcal polysaccharide vaccine in adults without a spleen.Am J Med. 1984; 76: 115-121Abstract Full Text PDF PubMed Scopus (41) Google Scholar]. Data on revaccination with these two vaccines are not available. The role of antibiotic prophylaxis in the management of splenectomized patients is controversial. The argument for chemoprophylaxis is that immunization does not cover all potential pathogenic serotypes and does not completely compensate for the loss of the splenic filter. Cases of fatal septicemia have been reported despite full courses of vaccination [44Sumaya CV Harbison RW Bretton HA Pneumococcal vaccine failures.Am J Dis Child. 1981; 135: 155-158Crossref PubMed Scopus (9) Google Scholar]. The antibiotics usually used are oral penicillin or erythromycin. Amoxycillin may be a better choice than penicillin, as it has better oral bioavailability and is a broader-spectrum agent. Prophylactic penicillin has been shown to be valuable in reducing pneumococcal sepsis by over 80% in children with sickle cell disease [45Gaston MH Venton JI Woods G et al.Prophylaxis with oral penicillin in children with sickle cell anaemia.N Engl J Med. 1986; 314: 1593-1599Crossref PubMed Scopus (874) Google Scholar], but it is unclear whether these data can be extrapolated to asplenic patients. Recommendations for asplenic patients vary from lifelong daily penicillin in children or adults [46Murdock IA Dos Anjos R Continued need for penicillin prophylaxis after splenectomy.Arch Dis Child. 1990; 65: 1268-1269Crossref PubMed Scopus (5) Google Scholar] to the assertion that there is no evidence that antibiotic prophylaxis is needed in vaccinated patients, as vaccine failure is very rare [47Read RC Finch RG Prophylaxis after splenectomy.J Antimicrob Chemother. 1994; 33: 4-6Crossref PubMed Scopus (28) Google Scholar]. It is generally agreed that it should be given to children too young to mount a protective immunologic response to vaccination (all children under 5 years without a spleen) and recommendations in the UK are that daily oral penicillin should be given to children under 16 years [48Department of Health Asplenic patients and immununisation.CMO's Update. 1994; 1: 3Google Scholar]. It should also be given to patients with coexistent immunosuppressive disease, as they also will respond poorly to immunization, and to all adults for the first 2 years after splenectomy, when the risk of OPSI is greatest. An alternative approach, particularly in lowerrisk groups or those unable to take daily prophylaxis, is to issue patients with an emergency supply of an antibiotic to take if they develop a febrile illness or become unwell. Antibiotic prophylaxis has now been complicated by the emergence of resistance amongst potential pathogens, and a case of penicillin-resistant pneumococcal meningitis has been described in a patient on long-term ampicillin prophylaxis [49Chadwick PR Keaney MG Jones RA Meningitis due to penicillin-resistant Streptococcus pneumoniae occurring in a patient on long term ampicillin prophylaxis.J Infect. 1993; 27: 277-279Abstract Full Text PDF PubMed Scopus (3) Google Scholar]. Other failures of treatment have been due to non-compliance, which is not surprising, as long-term prophylaxis is unrealistic for many patients [50Zarrabi MH Rosner FJ Rarity of failure of penicillin prophylaxis to prevent postsplenectomy sepsis.Arch Intern Meu. 1986; 146: 1207-1209Crossref PubMed Scopus (23) Google Scholar]. Although trials are needed to define which groups are most likely to benefit from chemoprophylaxis and for how long they need to be treated, these are difficult to design because of the low incidence of OPSI. Education of clinicians and patients is also important in preventing OPSI, and, although protocols exist in many centers, studies have demonstrated deficiencies in advice given to patients by clinicians [51Deodhar HA Marshall RJ Barnes JN Increased risk of sepsis after splenectomy.Br Med J. 1993; 307: 1408-1409Crossref PubMed Scopus (66) Google Scholar] and in patient awareness of their increased risk of serious infection [52White KS Covington D Churchill P Maxwell JG Norman KS Clarey TV Patient awareness of health precautions after splenectomy.Am J Infect Control. 1991; 19: 36-41Abstract Full Text PDF PubMed Scopus (52) Google Scholar]. Patients need to be informed of their increased susceptibility to infection and advised to present early if they become unwell. Warning devices for patients are advocated and these include Medic-Alert necklaces/bracelets and cards. Hospital discharge letters should inform the general practitioner of the splenectomy, whether immunization has been given and whether chemoprophylaxis is indicated. In general it is recommended that all asplenic patients should receive immunization against Streptococcus pneumoniae, H. influenzae type b and N. meningitidis types A and C. Annual influenza vaccine is also often given. Prophylaxis with antibiotics should probably be given to all children under 5 years of age, to all adults for the first 2 years after surgery and for life to patients with underlying iummunosuppressive disease. The use of and duration of chemoprophylaxis in other groups remains controversial, and the long-term use of antibiotics is unacceptable and unrealistic for many patients. Patients should be aware of their increased risk of infection and should be advised to obtain early medical assessment if they become ill, and be trained in self-medication when they develop a febrile illness. They should take appropriate malarial prophylaxis and avoid contact with mosquitoes and ticks when traveling to areas endemic for malaria and babesiosis. Q1: a. True; b. False; c. True; d. True; e. False Q2: a. False; b. False; c. True; d. False; e. False Q3: a. True; b. True; c. True; d. False; e. True Q4: a. False; b. False, c. True; d. True; e. True Q5: a. True; b. True; c. False; d. True; e. False Q6: a. False; b. True; c. False; d. False; e. True Q7: a. True; b. False; c. True; d. False; e. False